1. Field And Object Of The Invention
The invention relates to a process for preparing racemic 4-hydroxyphenylglycine having the following structural formula: ##STR1## 4-Hydroxyphenylglycine is useful as an intermediate in the preparation of derivatives of penicillanic acid.
It is an object of the invention to provide a novel process for the preparation of 4-hydroxyphenylglycine.
A concomitant object of the invention is to provide such a process which is capable of yielding 4-hydroxyphenylglycine in a comparatively pure state, i.e., having an assay of at least 97 percent, and in good yield.
A further concomitant object of the invention is to provide such a process from which the formed 4-hydroxyphenylglycine can be isolated in a comparatively pure state and in good yield directly from the reaction mixture using standard procedures thus precluding the need for subsequent tedious separation and purification procedures.
2. Description of the Prior Art
Aminomethylation can be broadly characterized as consisting of the condensation of an aldehyde and ammonia, or a primary or secondary amine, either in the free base or salt form, with a compound having a reactive (acidic) hydrogen, resulting in electrophilic substitution of the latter compound. In the case where phenol is the reactive-hydrogen compound it is well known that the directing influence of the hydroxyl group in electrophilic substitutions is ortho/para and on a statistical basis ortho, i.e., 2-position, substitution would be expected to predominate over para, i.e., 4-position, substitution. That ortho substitution does in fact predominate in the aminomethylation of phenol is documented in the art [for example see Decombe, Chem. Abs., 27, 2941 (1933); Grillot et al., J. Amer. Chem. Soc., 67, 1968-69 (1945)]. Furthermore, it has previously been found that a similar aminomethylation type of reaction, namely the reaction of phenol, glyoxlic acid and a diamine at a pH between 8 and 10 gives rise to an appropriate 2-hydroxyphenylglycine derivative (Dexter, U.S. Pat. No. 2,824,128)--that is to say, the substitution of the phenolic nucleus occurs at the 2 (or ortho) position rather than the 4 (or para) position. A literature report which appears contrary, that is, appears to contradict art-established evidence that aminomethylation of phenol occurs predominantly at the ortho position, is Abdullaev et al., Chem. Abs. 60, 1627 (1964), wherein it is reported that a yield of 92% para-hydroxybenzylamine was obtained on condensation of paraformaldehyde and ammonia with phenol. However, when we repeated this reaction, following the identical procedure described by Abdullaev et al., very little, if any, para-hydroxybenzylamine was obtained as determined by means of standard thin layer chromatography technique by comparison of the reaction mixture with an authentic sample.